Combined assisted bone age assessment and adult height prediction methods in Chinese girls with early puberty: analysis of three artificial intelligence systems.

BACKGROUND: The applicability and accuracy of artificial intelligence (AI)-assisted bone age assessment and adult height prediction methods in girls with early puberty are unknown. OBJECTIVE: To analyze the performance of AI-assisted bone age assessment methods by comparing the corresponding methods for predicted adult height with actual adult height. MATERIALS AND METHODS: This retrospective review included 726 girls with early puberty, 87 of whom had reached adult height at last follow-up. Bone age was evaluated using the Greulich-Pyle (GP), Tanner-Whitehouse (TW3-RUS) and China 05 RUS-CHN (RUS-CHN) methods. Predicted adult height was calculated using the China 05 (CH05), TW3 and Bayley-Pinneau (BP) methods. RESULTS: We analyzed 1,663 left-hand radiographs, including 155 from girls who had reached adult height. In the 6-8- and 9-11-years age groups, bone age differences were smaller than those in the 12-14-years group; however, the differences between predicted adult height and actual adult height were larger than those in the 12-14-years group. TW3 overestimated adult height by 0.4±2.8 cm, while CH05 and BP significantly underestimated adult height by 2.9±3.6 cm and 1.3±3.8 cm, respectively. TW3 yielded the highest proportion of predicted adult height within ±5 cm of actual adult height (92.9%), with the highest correlation between predicted and actual adult heights. CONCLUSION: The differences in measured bone ages increased with increasing bone age. However, the corresponding method for predicting adult height was more accurate when the bone age was older. TW3 might be more suitable than CH05 and BP for predicting adult height in girls with early puberty. Methods for predicting adult height should be optimized for populations of the same ethnicity and disease.

[Helsmoortel-Van der Aa syndrome due to hotspot mutation of ADNP gene and a literature review].

OBJECTIVE: To summarize the clinical features and biological characteristics of Helsmoortel Van der Aa syndrome (HVDAS) due to hotspot mutations of the ADNP gene in order to facilitate early diagnosis. METHODS: Clinical data and result of genetic testing for a girl with HVDAS due to hotspot mutation of the ADNP gene was summarized. Related literature was also reviewed. RESULTS: The patient, a 2-year-old girl, had presented with growth retardation, facial dysmorphism, psychomotor and language delay and recurrent respiratory infections. Whole exome sequencing revealed that she has harbored a heterozygous c.2496_2499delTAAA (p.Asn832Lysfs*81) variant of the ADNP gene, which was not found in either of her parents. CONCLUSION: Although the typical features of the HVDAS have included intellectual disability and autism spectrum disorders, growth retardation and premature primary tooth eruption may also be present. In addition, the phenotypic difference among individuals carrying hot spot variants of the ADNP gene was not prominent.

Two cases of infantile-onset primary generalized glucocorticoid hypersensitivity and the effect of mifepristone.

BACKGROUND: Primary generalized glucocorticoid hypersensitivity (PGGH) is a very rare disease caused by terminal organ hypersensitivity to glucocorticoids for which the aetiology is unknown. The incidence of PGGH is extremely rare, especially in children. To date, the literatures about the etiology, prognosis and treatment of PGGH are scarce. Aim of the study is describing the cases of two Chinese children with infantile-onset PGGH in one family, one of whom died and one who was treated with mifepristone. They are the two youngest children with PGGH reported in the literature. CASE PRESENTATION: Two siblings with infantile-onset PGGH were affected in this family. The main manifestations of patient 1 were typical Cushing's syndrome-like manifestations, significantly aggravated symptoms after physiological doses of glucocorticoids and very low levels of serum cortisol and adrenocorticotropin hormone (ACTH) during attacks. After being diagnosed with PGGH, he was given guidance to avoid glucocorticoids and took mifepristone therapy for 5 months, and his symptoms improved. Patient 2 was the younger brother of patient 1, with similar manifestations to his brother at the age of 4 months. Patient 2 ultimately died at the age of 9 months. CONCLUSION: PGGH is a very rare disease that can lead to death if not diagnosed and treated in a timely manner. This article describes the cases of the two youngest children with PGGH reported in the literature, one of whom improved after mifepristone treatment, and increases the knowledge of the clinical manifestations of and the treatment experience in PGGH.

Factors affecting bone maturation in Chinese girls aged 4-8 years with isolated premature thelarche.

BACKGROUND: In isolated premature thelarche (IPT) girls, bone age (BA) is considered consistent with chronological age. However, some IPT girls confirmed by gonadotropin-releasing hormone (GnRH) stimulation test could show another trend. We analysed BA and possible potentiating factors in a selected group of girls aged 4-8 years with IPT. METHODS: IPT girls confirmed by GnRH stimulation test aged 4-8 years hospitalized from January 2015 to April 2018 at Shenzhen Children's Hospital were included in this retrospective study. They were divided into two groups with advanced BA of 2 years as the cut-off. Body mass index (BMI) and hormone levels were the main outcome measures, and regression analysis was used to identify independent risk factors. IPT girls were divided into subgroups according to the levels of BMI standard deviation score (SDS), insulin-like growth factor-1 (IGF-1) SDS and dehydroepiandrosterone sulfate (DHEAS) SDS for comparisons of advanced BA. RESULTS: Overall, 423 subjects were included and classified into the advanced BA group (48.7%, n = 206) and control group (51.3%, n = 217). The advanced BA group had significantly higher BMI SDS, serum DHEAS SDS, IGF-1 SDS, androstenedione and fasting insulin and significantly lower sex hormone binding globulin (all p < 0.001). Serum IGF-1 SDS (OR = 1.926, p<0.001), BMI SDS (OR = 1.427, p = 0.001) and DHEAS SDS (OR = 1.131, p = 0.005) were independent risk factors for significantly advanced BA. In the multiple linear regression model, serum IGF-1 SDS, BMI SDS and DHEAS SDS were the strongest predictors of advanced BA, accounting for 19.3% of the variance. According to BMI, 423 patients were classified into three groups: normal weight (56.03%, n = 237), overweight (19.15%, n = 81) and obesity (24.82%, n = 105). The proportion of advanced BA in obesity group was significantly higher than those of normal weight and overweight groups (χ2 = 18.088, p<0.001). In the subgroup with normal weight, higher serum IGF-1 SDS (p = 0.009) and DHEAS SDS (p = 0.003) affected BA advancement independent of BMI SDS. CONCLUSIONS: Girls with IPT confirmed by GnRH stimulation test aged 4-8 years might have significantly advanced BA. Obesity was highly associated with advanced BA. Age-specific serum IGF-1 SDS and DHEAS SDS were risk factors for BA advancement independent of BMI.

Investigation into the Structure and Properties of Biochar Co-Activated by ZnCl2 and NaHCO3 under Low Temperature Conditions.

Using sodium lignosulfonate as feedstock, ZnCl2 and NaHCO3 co-activated the hierarchical porous carbons (HPCs) were prepared by one-pot pyrolysis with different NaHCO3 dosages (0-4 g) and carbonization temperatures (400-600 °C). Subsequently, phosphotungstate (HPW) was supported with the resulting biochar for the α-pinene hydration reaction to produce α-terpineol. The optimum preparation conditions were determined according to the yield of α-terpineol. The formation mechanism and physicochemical properties of HPCs were analyzed through TG, SEM, XPS, XRD, FT-IR, and N2 adsorption-desorption isotherms. The results demonstrated that NaHCO3 underwent a two-step reaction which liberated a substantial quantity of CO2, thereby enhancing activated carbon's macroporous and mesoporous structures. Simultaneously, NaHCO3 mitigated strong acid gas (HCl) emissions during ZnCl2 activation. Compared with AC450-4:8:0 prepared by ZnCl2 activation alone, the total pore volume of AC450-4:8:2 prepared by co-activation is increased from 0.595 mL/g to 0.754 mL/g and the mesopore rate from 47.7% to 77.8%, which is conducive to reducing the steric hindrance of the hydration reaction and improving the selectivity. Hydration experiments show that the selectivity of α-terpineol is 55.7% under HPW/AC450-4:8:2 catalysis, higher than 31.0% for HPW and 47.4% for HPW/AC450-4:8:0.

Pattern of linear growth and progression of bone maturation for girls with early-onset puberty: A mixed longitudinal study.

Background and objective: With a worldwide trend to earlier age of onset of puberty, the prevalence of early-onset puberty (EP) among girls has increased. The impact of EP on the pattern of linear growth and bone maturation is unclear. Accordingly, the objective of our study was to describe this pattern for girls with EP in Shenzhen, China. Methods: A total of 498 untreated girls diagnosed with EP at Shenzhen Children's Hospital, China, between January 2016 and December 2021. A total of 1,307 anthropometric measurements and 1,307 left-hand radiographs were available for analysis. Artificial intelligence (AI) was used to determine bone age (BA). Participants were classified into groups according to chronological age (CA) and BA. The pattern of linear growth (height) and progression of bone maturation was described between groups using the Lambda-Mu-Sigma (LMS) method. Published height-for-CA and height-for-BA norm references for a healthy Chinese population were used for age-appropriate comparisons. Results: The mean CA of appearance of first pubertal signs (breast buds) was 8.1 ± 0.5 years. Compared to norm-referenced data, girls with EP were significantly taller at a CA of 7-10 years. This was followed by a slowing in linear growth after a CA of 10 years, with 71 girls with EP having already achieved their target adult height. From 7 to 10 years of BA, the linear growth was slower in the EP group compared to norm-reference values. This was followed by a period of catch-up growth at 11.2 years of BA, with growth curves approaching norm-referenced values. The BA progressed rapidly from 7 to 8 years of age in about half of the girls with EP (median ΔBA/ΔCA >1.9), slowing, thereafter, until the period of catch-up growth at 11.2 years of BA. Conclusions: BA provides a more reliable reference than CA to assess growth parameters among girls with EP. Our limited data set does indicate that EP does not negatively impact final adult height. Therefore, the growth curves from our study are relevant, providing a reference for pediatricians in this clinical population and, thus, preventing over-treatment for EP.

Secondary oxidized di-2-ethylhexyl phthalate metabolites may be associated with progression from isolated premature thelarche to central precocious or early puberty.

Phthalate esters (PAEs) may act as estrogen receptor agonists, and their relationship with precocious puberty is a global health concern. However, their role in isolated premature thelarche (IPT) progression remains unclear. We conducted a cohort study investigating the relationship between IPT progression and urinary PAE metabolites. Girls with IPT aged 6-8 years were regularly followed up every three months for one year. Clinical data and urine PAE metabolite levels were collected. Participants who progressed to central precocious puberty (CPP) or early puberty (EP) had significantly higher ovarian volume, breast Tanner stage, and levels of the creatinine-adjusted urinary secondary oxidized di-2-ethylhexyl phthalate (DEHP) metabolites (Σ4DEHP). Breast Tanner stage (odds ratio [OR] = 7.041, p = 0.010), ovarian volume (OR = 3.603, p = 0.019), and Σ4DEHP (OR = 1.020, p = 0.005) were independent risk factors for IPT progression. For each 10 µg/g/Cr increase in the urine level of Σ4DEHP, the risk of progression from IPT to CPP/EP within one year increased by 20%. This study demonstrated that the breast Tanner stage, ovarian volume, and Σ4DEHP in urine were independent risk factors for IPT progression, and Σ4DEHP may be associated with the progression of IPT to CPP or EP.

Association between phthalate exposure and accelerated bone maturation in Chinese girls with early puberty onset: a propensity score-matched case-control analysis.

Estrogen can promote the acceleration of bone maturation and phthalate esters (PAEs) have estrogen-mimicking effects. We investigated whether PAEs are associated with the acceleration of bone age (BA) in girls with early onset of puberty (EOP). This case-control study enrolled 254 girls with EOP from the Endocrinology Department at Shenzhen Children's Hospital between December 2018 and August 2019. Ultra-performance liquid chromatography and tandem mass spectrometry were used to analyze the 10 metabolites of PAEs (mPAEs) in urine samples. BA was measured using an artificial intelligence system. BA exceeding the chronological age (CA) by > 2 years (BA-CA ≥ 2 years) was referred to as significant BA advancement. Participants were divided into groups A (BA-CA ≥ 2 years; case group) and B (BA-CA < 2 years; control group). Propensity score matching (PSM) was performed for both groups in a 1:2 ratio with a caliper of 0.25. To identify potential dose-response relationships between PAEs exposure and BA advancement, we grouped the participants after PSM according to the tertiles of the mPAE concentrations. After PSM, 31 and 62 girls in groups A and B were selected. The concentration of Mono-ethyl phthalate (MEP) in group A was significantly higher than in group B (11.83 µg/g vs. 7.11 µg/g, P < 0.05); there was no significant difference in the levels of other mPAEs between the groups. The degree of BA advancement and proportion of significantly advanced BA in the lowest, middle, and highest tertiles of the MEP sequentially increased, as well as in the lowest, middle, and highest tertiles of Mono-(2-ethyl-5-carboxypentyl) phthalate; however, these were only statistically different between the highest and lowest MEP tertiles (both P < 0.05). For the remaining mPAEs, differences in the degree of BA advancement among the lowest, middle, and highest tertiles, as well as differences in the proportion of significantly advanced BA among the lowest, middle, and highest tertiles, were not significant (all P > 0.05). Our findings suggested that MEP was positively associated with BA advancement in girls with EOP. Exposure to PAEs may promote accelerated bone maturation.

Evaluation on clinical efficacy of Fuzheng Jiedu Huayu Decoction combined with antibiotics in the treatment of pneumonia in the elderly - A multi-center, double-blind, parallel, randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of Fuzheng Jiedu Huayu Decoction (FJHD) in treating pneumonia in the elderly. METHODS: Adopting a multi-center, double-blind, parallel, randomized controlled trial, 284 elderly pneumonia patients were enrolled and randomly allocated to the standard treatment with FJHD (treatment group, TG) and the standard treatment with placebo group (control group, CG). Efficacy and safety was evaluated through mortality rate, curative rate, symptom improvement, chest X-ray (CXR) lesion absorption, arterial blood gas (ABG), peripheral blood leukocyte count (PBLC) and adverse events. RESULTS: There was no significant difference in mortality rate between both groups (P > 0.05). TG significantly enhanced the curative rate of a 2-week treatment course (P < 0.05). Compared with CG, TG significantly decreased the expectoration score during the first and second week of treatment (P < 0.05). During the first week, improvement in expectoration was conducive to airway patency. During the second week, wheezing, shortness of breath and other symptoms were also significantly improved. During the third week, body temperature was stable. TG improved lesion absorption with Pneumonia Severity Index (PSI) class II (P < 0.05) and SMART-COP score 1 (P < 0.05). TG significantly decreased the arterial carbon dioxide partial pressure after a 1-week treatment. There were no serious adverse events in TG. CONCLUSION: Standard anti-infection treatment with FJHD is a safe and reliable method of treating elderly patients with pneumonia, improving the curative effect after a 2-week treatment course, ameliorating expectoration and promoting the absorption of pneumonia lesions.

Association between skin reactions and efficacy of summer acupoint application treatment on chronic pulmonary disease: A prospective study.

OBJECTIVE: To examine the variations in the prevalence of skin reactions and the association between skin reactions and efficacy of summer acupoint application treatment (SAAT) on chronic pulmonary disease (CPD). METHODS: A total of 2,038 patients with CPD were enrolled at 3 independent hospitals (defined as Groups A, B and C, respectively) in China. All patients were treated by SAAT, as applying a herbal paste onto the acupoints of Fengmen (BL 12) and Feishu (BL 13) on the dog days of summer, according to the lunar calendar, in 2008. Ten days after treatment, skin reaction data (no reaction, itching, stinging, blistering, and infection) were obtained via face-to-face interviews. Patients were retreated in the same hospital one year later, thereby allowing doctors to assess treatment efficacy based on the patients' symptoms, the severity of the spirometric abnormalities, and the concomitant medications used. RESULTS: A large number of patients (85.3%) displayed reactive symptoms; however, the marked associations between reactive symptoms and age or gender were not observed. An increased number of patients from Group B (99.3%) and Group C (76.5%) displayed reactive symptoms due to the increased mass of crude Semen Sinapis Albae. The effective rate of SAAT was as high as 90.4% for patients of Group B, which was followed by Group A (70.9%) and Group C (42.2%). Using stratified analyses, a convincing association between reactive symptoms and therapeutic efficacy was observed for patients with asthma [itching: odds ratio (OR)=2.17, 95% confidence interval (CI): 1.49 to 3.14; blistering: OR=0.43, 95% CI: 0.25 to 0.73; and no reaction: OR=0.56, 95% CI: 0.35 to 0.90]. However, the same tendency was not observed for patients with chronic bronchitis and chronic obstructive pulmonary disease. CONCLUSIONS: SAAT can induce very mild skin reactions for patients with CPD, among which patients with asthma displayed a strong association between skin reactions and therapeutic efficacy. The skin reactions may be induced by the crude Semen Sinapis Albae.